The present invention relates, in general, to apparatus for coupling a capillary electrophoresis system to a mass spectrometer, and more particularly to an improved interface therefor.
Capillary electrophoresis devices are commonly used to separate electrically charged particles or molecules in solution or suspension in the presence of an applied electric field, with the particles moving toward the electrodes of opposite electrical polarity. Detection of the particles has been by the use of optical detectors based on ultraviolet absorbance and fluorescence emission, but mass spectrometry now fulfills the need for universal detection and high sensitivity. Accordingly, the solution with the entrained particles; i.e., the analytes, is directed to an atmospheric pressure ionization mass spectrometer for analysis to identify the compound or compounds in the solution. Since the mass spectrometer requires an input in the form of gas-phase ions, the analyte from the electrophoresis system has been transferred in this condensed phase from an electrophoresis capillary through a mechanism for producing ion evaporation by thermospray, fast atom bombardment, matrix-assisted laser desorption or electrospray, to the mass spectrometer. Thermospray has not been feasible because of the high liquid flow rates required for thermospray ionization and because of sensitivity limitations in comparison to other mass spectrometry ionization techniques. Fast atom bombardment techniques produce excessive band-broadening and loss of separation efficiency. Also, matrix-assisted laser desorption has so far enjoyed limited success for on-line capillary electrophoresis-mass spectrometry coupling. Finally, electrospray ionization benefits from high electrophoresis electroosmotic flows and low buffer concentrations to maintain stable electrospray conditions. Thus, the coupling of a capillary electrophoresis system to a mass spectrometer presents demanding challenges involving maintenance of flow rates while transferring an analyte from a small-diameter outlet capillary tube to an inlet, or sprayer capillary leading to the mass spectrometer.
One coupling system which attempted to meet the problems is described by J. A. Oliveres, et al in Analytical Chemistry, 59 (1987) pages 1230-1232, which describes a "sheath flow" system. However, it has been found that the sheath flow approach can suffer from incomplete mixing of the sheath and analyte, leading to ion current instability. Another approach, described by E. D. Lee et al, Biomed Environ. Mass Spectrom, 18 (1989) pages 844-850, provided a liquid junction wherein the capillary outlet from a capillary electrophoresis (CE) device is placed opposite the end of the capillary electrode of an ion spray liquid chromatograph/mass spectrometer interface device, with a 10-25 .mu.m gap between the two pieces. The gap allowed "make-up" buffer to flow unrestricted into the ion spray interface electrode from a surrounding reservoir, preventing suction from occurring at the end of the CE device capillary. Since the flow rate into the ion spray interface was 10-20 times greater than the flow from the CE capillary, analytes from the capillary were rapidly swept into the mass spectrometer by the buffer. However, this approach required a high degree of precision in aligning and spacing the electrophoresis capillary and the sprayer.